Cooling analgesia harnessed to relieve chronic pain

By experimentally activating a special protein involved in mediating sensations of coolness, researchers have made a breakthrough in understanding how the body's nervous system can be stimulated to relieve chronic pain. The findings are reported by a team led by Susan Fleetwood-Walker and Rory Mitchell of University of Edinburgh and appear in the August 22nd issue of the journal Current Biology, published by Cell Press.

Ancient Greek physicians knew of the benefits of cooling to relieve pain, and many traditional remedies use mint oil for relieving pain, but it is only now, in the 21st century, that a mechanism for such analgesic effects has been identified.

In their new work, the researchers looked for ways to relieve chronic pain in rats, and they found that certain cooling chemicals, either injected or simply applied in small doses to the skin, have a dramatic natural painkilling effect. The researchers showed that the analgesic effect occurs through activation of a recently identified protein, called TRPM8, that is expressed in nerve cells in the skin and responds to both cool temperatures and cooling chemicals, such as the active ingredients in mint.

TRPM8 belongs to an interesting class of proteins whose members mediate the sensation of diverse stimuli, including taste, temperature, and touch.

Approaches using cooling compounds that activate the TRPM8 protein could be used for chronic pain patients--for example, in treating neuropathic pain and arthritis in cases where conventional painkillers have little effect or are of limited use as a result of side effects. Such therapies would make use of the body's own capacity to suppress pain. The discovery of a novel biological mechanism by which cooling analgesia works therefore has great potential for relieving the suffering of millions of chronic pain patients.

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The researchers include Clare J. Proudfoot, Emer M. Garry, David F. Cottrell, Roberta Rosie, Heather Anderson, Darren C. Robertson, and Susan M. Fleetwood-Walker of University of Edinburgh, Summerhall in Edinburgh, UK; Rory Mitchell of University of Edinburgh in Edinburgh, UK.

This work was supported by Wellcome Trust grants to S.F.-W. and R.M. and a Medical Research Council (MRC) Studentship to C.P.